Xenobiotic-induced thyroid and steroid hormone disruption in humans and wildlife – University of Copenhagen

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Department of Pharmacy > Research > Section of Analytical Biosciences > Toxicology Lab > Xenobiotic

Xenobiotic-induced thyroid and steroid hormone disruption in humans and wildlife

 

Using interdisciplinary tools between analytical chemistry, toxicology, environmental chemistry and endocrinology this project investigates xenobiotics (e.g. pharmaceuticals and environmental contaminants) that pose a risk to humans and wildlife at the very forefront of endocrine-disruption research. Highly sensitive vertebrate indicator species are being used in the study; African clawed frog (Xenopus laevis), California sea lion (Zalophus californianus), killer whale (Orcinus orca) and polar bear (Ursus maritimus).

Thyroid and steroid hormone systems are most often studied independently, but as the endocrine axes (figure) are interwoven, it is fundamentally important to investigate the two in union to fully understand the impacts of xenobiotics. To date, much of the research focusing on endocrine disruption has mainly considered the interruption of steroid estrogens and androgens. Here, I focus on using cell systems and animal models expressing thyroid and steroid hormones. 

 

 

 

 

 

 

 

 

 


As illustrated in the figure, steroid hormones are regulated by complex feedback systems in the HPA and HPG axes, and thyroid hormones are regulated in the HPT axis. The axes can influence each other by cross-talk from hormones or hormone-mimicking compounds. Several xenobiotics, many of anthropogenic origin, are known to disrupt these finely tuned processes, interfering with hormone homeostasis and causing severe adverse effects.

Methods
*In-vitro (thyroid gland explant culture, H295R steroidogenesis cell-line) and in-vivo (X. laevis) models.
*Immunohistochemistry (UC Berkeley).
*Real-time polymerase chain reaction (qPCR) is used to assess mRNA changes in target enzymes, transporters and receptors.
*Steroid hormones are analysed by GC-EI-MS/MS (Uni Copenhagen).
*Thyroid hormones are analysed by LC-AJS-MS/MS (UC Berkeley).